Docetaxel and carboplatin combination chemotherapy as outpatient palliative therapy in carcinoma of unknown primary: a multicentre Hellenic Cooperative Oncology Group phase II study (Journal article)

Pentheroudakis, G./ Briasoulis, E./ Kalofonos, H. P./ Fountzilas, G./ Economopoulos, T./ Samelis, G./ Koutras, A./ Karina, M./ Xiros, N./ Samantas, E./ Bamias, A./ Pavlidis, N.

INTRODUCTION: Taxane/platinum combinations exhibit synergistic cytotoxicity and activity against a broad range of solid tumours. We sought to optimise the regimen as a suitable outpatient palliative treatment for cancer of unknown primary (CUP). PATIENTS AND METHODS: Eligible CUP patients with adenocarcinoma or poorly differentiated carcinoma, performance status of 0-2, adequate organ function and assessable disease were treated with docetaxel 75 mg/m(2) and carboplatin at an area under the concentration time-curve (AUC) of 5, both as 30-minute intravenous infusions, every three weeks. Patients with isolated axillary adenopathy, squamous cell cervical or inguinal adenopathy and PSA or germ-cell serum tumour markers were excluded. RESULTS: Forty-seven patients entered the trial, 24 with predominantly nodal disease or non-mucinous peritoneal carcinomatosis (favourable risk) and 23 with visceral metastases (unfavourable risk). A median of 6 cycles of chemotherapy were administered, with relative dose intensities of both drugs >90%. Response rates were 32% (46% in favourable risk, 17% in unfavourable), comparable to the activity of paclitaxel/platinum regimes, though complete remissions were seen only in favourable risk patients. Granulocyte-colony stimulating factor support was used in a third of treatment cycles. Toxicity was mild and manageable, with grade 3-4 neutropenia in 26% of patients, febrile neutropenia in 7% and severe non-hematologic side-effects in less than 8% of patients. No toxic deaths or severe neurotoxicity were seen. Median time to progression (TTP) and overall survival (OS) were 5.5 and 16.2 months respectively. Survival was driven mainly by favourable-risk patients (22.6 months), as those with visceral metastases had a poor median survival of only 5.3 months. Good performance status and low-volume disease predicted for superior outcome, while docetaxel relative dose-intensity was a positive prognosticator only in favourable-risk patients. CONCLUSIONS: One-hour docetaxel/carboplatin is a convenient, safe and effective outpatient palliative treatment for CUP patients, providing meaningful survival prolongation only in favourable-risk patients. Insights in the molecular biology of CUP are needed for the development of targeted therapeutic manipulations of malignant resistance and progression.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: Adenocarcinoma/*drug therapy,Adult,Aged,*Ambulatory Care/methods,Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use,Area Under Curve,Carboplatin/administration & dosage,Carcinoma/*drug therapy,Disease Progression,Disease-Free Survival,Drug Administration Schedule,Female,Greece,Humans,Infusions, Intravenous,Kaplan-Meier Estimate,Lymphatic Metastasis,Male,Middle Aged,Neoplasms, Unknown Primary/*drug therapy/pathology,*Outpatients,Palliative Care/*methods,Peritoneal Neoplasms/drug therapy/secondary,Predictive Value of Tests,Prognosis,Risk Factors,Taxoids/administration & dosage,Treatment Outcome
ISSN: 1651-226X
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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